Factor VIII(Intas Biopharmaceuticals Ltd.)

New Seven-Year Follow-Up Phase 2 Study Results Showed Durable Hemostatic Benefit for Adults with Severe Hemophilia A SAN RAFAEL, Calif., Feb. 6, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN), a global biotechnology company dedicated to transforming lives through genetic discovery, today announced that new data on ROCTAVIAN™ (valoctocogene roxaparvovec-rvox) will be presented at the 2024 European Association for Haemophilia and Allied Disorders (EAHAD) Congress, Feb. 6-9, 2024. Results from a Phase 2, open-label study of ROCTAVIAN showed that median factor VIII (FVIII) activity at year seven remained in the mild hemophilia range (10.3 IU/dL per chromogenic assay), and mean annualized bleeding rate (ABR) for treated bleeds over the full follow-up period decreased by 96% from baseline for adults with severe hemophilia A in the 6x1013 vg/kg dose cohort. The majority of participants maintained hemostasis, with only two of the seven participants in the study returning to regular prophylaxis, and no new safety signals emerged. These data will be presented as a poster presentation from 6:30-7:30 p.m. Central European Time (CET) on Wednesday, Feb. 7. "People living with severe hemophilia A face a lifelong treatment burden, including frequent injections or infusions and a high risk of health complications like uncontrolled bleeding and irreversible joint damage, which may persist despite good adherence to prophylactic therapy," said Hank Fuchs, M.D., President of Worldwide Research and Development at BioMarin. "We are pleased to present data showing the impact of one-time treatment with ROCTAVIAN over seven years following the infusion, underscoring the potential of gene therapy to make a meaningful and long-lasting impact for people living with severe hemophilia A." Additional studies will be shared during oral presentations on Friday, Feb. 9 from 8:30-10:00 a.m. CET, including preliminary results from GENEr8-INH, a Phase 1/2 study evaluating the safety and efficacy of ROCTAVIAN in participants with active and prior FVIII inhibitors, as well as one-year results from GENEr8-3, a Phase 3b study evaluating the use of prophylactic corticosteroids with ROCTAVIAN treatment. BioMarin's key presentations at EAHAD include: Poster Presentations: Seven-year follow-up of valoctocogene roxaparvovec gene therapy for haemophilia A #PO124 Wednesday, Feb. 7, 2024, 6:30-7:30 p.m. CET Treatment preferences in people with severe haemophilia A: a discrete choice experiment in the United States #PO314 Wednesday, Feb. 7, 2024, 6:30-7:30 p.m. CET Health-related quality of life and long-term joint damage in people with severe haemophilia A in Brazil #PO144 Wednesday, Feb. 7, 2024, 6:30-7:30 p.m. CET Oral Presentations: Safety and efficacy of valoctocogene roxaparvovec in participants with active and prior FVIII inhibitors: preliminary results from GENEr8-INH, a phase 1/2 study #OR10 Friday, Feb. 9, 2024, 8:30-10:00 a.m. CET Safety and efficacy of valoctocogene roxaparvovec with prophylactic corticosteroids: 1-year GENEr8-3 results #OR02 Friday, Feb. 9, 2024, 8:30-10:00 a.m. CET Human liver biopsy analysis reveals lower RNA transcription may contribute to a decline in FVIII levels following AAV5-hFVIII-SQ gene therapy #OR06 Friday, Feb. 9, 2024, 8:30-10:00 a.m. CET About Hemophilia A Hemophilia A, also called factor VIII (FVIII) deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective FVIII, a clotting protein. Although it is passed down from parents to children, about one-third of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have hemophilia A. About ROCTAVIAN ROCTAVIAN is an adeno-associated virus vector-based gene therapy used for the treatment of adults with severe hemophilia A who do not have antibodies to adeno-associated virus serotype 5 (AAV5), which is determined by a blood test. The one-time infusion works by delivering a functional gene that is designed to enable the body to produce FVIII on its own, reducing the need for ongoing prophylaxis. The European Commission (EC) granted conditional marketing authorization to ROCTAVIAN on August 24, 2022. The U.S. Food and Drug Administration (FDA) approved ROCTAVIAN on June 29, 2023. More information on testing to determine eligibility to receive ROCTAVIAN can be found at in the U.S. and in Germany. U.S. Important Safety Information ROCTAVIAN U.S. Important Safety Information Contraindications: Patients with active infections, either acute (such as acute respiratory infections or acute hepatitis) or uncontrolled chronic (such as chronic active hepatitis B). Patients with known significant hepatic fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent), or cirrhosis, and patients with known hypersensitivity to mannitol. Infusion-related reactions including hypersensitivity reactions and anaphylaxis, have occurred. Monitor during and for at least 3 hours after ROCTAVIAN administration. Administer ROCTAVIAN in a setting where personnel and equipment are immediately available to treat infusion-related reactions. Discontinue infusion for anaphylaxis. Hepatotoxicity: The safety and effectiveness of ROCTAVIAN in patients with hepatic impairment has not been established. Perform liver health assessments prior to administration. The majority of patients treated with ROCTAVIAN experienced ALT elevations and required corticosteroids for ALT elevation. Assess patient's ability to receive corticosteroids and/or other immunosuppressive therapy that may be required for an extended period. Live vaccines should not be administered to patients while on immunosuppressive therapy. Monitor ALT weekly for at least 26 weeks and as clinically indicated, during corticosteroid therapy and institute corticosteroid treatment in response to ALT elevations as required. Continue to monitor ALT until it returns to baseline. Monitor factor VIII activity levels since ALT elevation may be accompanied by a decrease in factor VIII activity. One case of autoimmune hepatitis was reported during third year follow-up in a patient with history of hepatitis C and steatohepatitis. It is recommended that patients abstain from consuming alcohol for at least 1 year after administration and thereafter limit alcohol use. Concomitant medications may cause hepatotoxicity, decrease factor VIII activity, or change plasma corticosteroid levels which may impact liver enzyme elevation and/or factor VIII activity or decrease the efficacy of the corticosteroid regimen or increase their side effects. Closely monitor concomitant medication use including herbal products and nutritional supplements and consider alternative medications in case of potential drug interactions. Thromboembolic events: Factor VIII activity above ULN has been reported following ROCTAVIAN infusion. Thromboembolic events may occur in the setting of elevated factor VIII activity above ULN. Evaluate patients for risk of thrombosis including general cardiovascular risk factors before and after administration of ROCTAVIAN. Advise patients on their individual risk of thrombosis in relation to their factor VIII activity levels above ULN and consider prophylactic anticoagulation. Advise patients to seek immediate medical attention for signs or symptoms indicative of a thrombotic event. Factor VIII inhibitors and Monitoring for inhibitors: The safety and effectiveness of ROCTAVIAN in patients with prior or active factor VIII inhibitors have not been established. Patients with active factor VIII inhibitors should not take ROCTAVIAN. Following administration, monitor patients for factor VIII inhibitors (neutralizing antibodies to factor VIII). Test for factor VIII inhibitors especially if bleeding is not controlled, or plasma factor VIII activity levels decrease. Monitor Factor VIII using the same schedule for ALT monitoring. It may take several weeks after ROCTAVIAN infusion before ROCTAVIAN-derived factor VIII activity rises to a level sufficient for prevention of spontaneous bleeding episodes. Exogenous factor VIII or other hemostatic products may also be required in case of surgery, invasive procedures, trauma, or bleeds. Consider more frequent monitoring in patients with factor VIII activity levels ≤ 5 IU/dL and evidence of bleeding, taking into account the stability of factor VIII levels since the previous measurement. Factor VIII activity produced by ROCTAVIAN in human plasma is higher if measured with one-stage clotting assays compared to chromogenic substrate assays. When switching from hemostatic products prior to ROCTAVIAN treatment, physicians should refer to the relevant prescribing information to avoid the potential for factor VIII activity assay interference during the transition period. Malignancy: The integration of liver-targeting AAV vector DNA into the genome may carry the theoretical risk of hepatocellular carcinoma development. ROCTAVIAN can also insert into the DNA of other human body cells. Monitor patients with risk factors for hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age) with regular liver ultrasound (e.g., annually) and alpha-fetoprotein testing for 5 years following ROCTAVIAN administration. In the event that any malignancy occurs after treatment with ROCTAVIAN, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100. Most Common Adverse Reactions: Most common adverse reactions (incidence ≥ 5%) were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain. Most common laboratory abnormalities (incidence ≥ 10%) were ALT, AST, LDH, CPK, factor VIII activity levels, GGT and bilirubin > ULN. Patients also experienced adverse reactions from corticosteroid use. Isotretinoin, Efavirenz, and HIV Positive Patients: Isotretinoin is not recommended in patients who are benefiting from ROCTAVIAN. Efavirenz is not recommended in patients treated with ROCTAVIAN. Clinical studies of ROCTAVIAN did not include sufficient numbers of patients with HIV to determine whether the efficacy and safety differs compared to patients without HIV infection. Females and Males of Reproductive Potential: ROCTAVIAN is not intended for administration in women. There are no data on the use of ROCTAVIAN in pregnant women or regarding lactation. For 6 months after administration of ROCTAVIAN, men of reproductive potential and their female partners must prevent or postpone pregnancy using an effective form of contraception, and men must not donate semen. You may report side effects to the FDA at (800) FDA-1088 or . You may also report side effects to BioMarin at 1-866-906-6100. Please see the ROCTAVIAN full Prescribing Information for additional Important Safety Information. About BioMarin Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: the data BioMarin plans to present at the 2024 European Association for Haemophilia and Allied Disorders (EAHAD) Congress, including the three oral and three poster presentations; the development of BioMarin's ROCTAVIAN program; the potential impact and benefits of ROCTAVIAN for people with severe hemophilia A; and the continued clinical development of ROCTAVIAN. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: BioMarin's success in the commercialization of ROCTAVIAN, including achieving adequate market share and reimbursement levels; whether ROCTAVIAN will have the impacts and benefits as anticipated; the results and timing of current and planned preclinical studies and clinical trials of ROCTAVIAN and the release of data from those trials, including continued monitoring of the participants in the clinical trials and post-approval studies; BioMarin's ability to successfully manufacture ROCTAVIAN for the clinical trials and commercially; the content and timing of decisions by the FDA, EU health authorities and other regulatory authorities regarding ROCTAVIAN; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin® is a registered trademark of BioMarin Pharmaceutical Inc. ROCTAVIAN™ is a trademark of BioMarin Pharmaceutical Inc. in the United States. Company Codes: NASDAQ-NMS:BMRN

Studies point to preventive measures and therapies that can set children on a healthier course with lifelong benefits SAN DIEGO, Dec. 9, 2023 /PRNewswire/ -- Researchers report significant progress toward improving access to effective interventions to address blood disorders and promote healthy blood cell functioning in four studies presented during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition. The studies suggest new opportunities to act early in life to achieve lifelong benefits, including in children born with challenging disorders such as sickle cell disease (SCD) and hemophilia. "This research really highlights the importance of early action and prevention," said Sarah O'Brien, MD, of Nationwide Children's Hospital. "From prenatal supplements to optimizing therapies, these findings show ways we can help our young patients be as healthy as possible, which can also improve outcomes with more complex therapies." The first two studies examine life-changing therapies for people living with SCD, an inherited blood disorder that affects the blood's ability to carry oxygen, leading to organ damage and episodes of severe pain called vaso-occlusive crises. One provides new evidence that hydroxyurea, an oral medication widely available in the U.S. and other high-resource countries, is feasible, safe, and effective to administer at optimal doses in Africa, where many people with sickle cell currently lack access to treatment. The other study reports substantial and long-lasting benefits of a gene therapy for SCD, reflected not only in laboratory markers but in significant improvements in quality of life for people living with the disorder. The third study sheds light on how the amount of folic acid, or folate, a developing fetus is exposed to in the womb can affect the system that maintains blood and immune cells in adulthood, with important implications for lifelong health. The fourth study shows that a drug injected subcutaneously can help protect infants born with the bleeding disorder hemophilia from serious complications such as intracranial bleeds. Avoiding such events at an early age can reduce children's chances of permanent brain and tissue damage and potentially set them up to receive the greatest possible benefit from other therapies later in life. Lovo-cel gene therapy shows enduring results in preventing sickle cell pain crises 1051: Efficacy, Safety, and Health-Related Quality of Life (HRQOL) in Patients with Sickle Cell Disease (SCD) Who Have Received Lovotibeglogene Autotemcel (Lovo-cel) Gene Therapy: Up to 60 Months of Follow-up In the longest-running gene therapy trial for SCD to date, researchers report that a vast majority of patients have seen long-lasting, nearly complete resolution of vaso-occlusive events. With up to five years of follow-up and a median follow-up of three years, the new findings bolster evidence that lovo-cel is a safe and effective treatment for SCD. "It is a truly transformative therapy," said Julie Kanter, MD, director of the Adult Sickle Cell Disease Program and professor of Medicine and Pediatrics at University of Alabama, Birmingham, and the study's lead author. "Using gene therapy through lovo-cel, we've been able to essentially rid individuals with SCD of vaso-occlusive events. It results in normal hemoglobin levels and people just feeling amazing." SCD is caused by a gene that results in the production of abnormal hemoglobin, a protein in the red blood cells that carries oxygen. For lovo-cel therapy, stem cells are removed from a patient's bone marrow and a viral vector is used to add a gene to the stem cells that equips them to produce healthy hemoglobin. The modified stem cells are then returned to the bone marrow, where they manufacture blood cells with healthy hemoglobin. Several other gene therapies for SCD are being tested in separate clinical trials. Lovo-cel is the longest running gene therapy trial for SCD to date and the only current trial to use a gene addition therapy rather than gene editing techniques to alter the stem cell genome. The new findings include results from 34 pediatric and adult patients who completed lovo-cel therapy within the past 16 months to five years. Between six and 18 months following their lovo-cel infusion, 88.2% of the patients experienced no vaso-occlusive events at all and 94.1% experienced no severe vaso-occlusive events. By contrast, these patients suffered a median of three severe vaso-occlusive events per year for the two years before they enrolled in the trial. A vast majority of patients showed significant amounts of new, non-sickle hemoglobin (HbAt87Q) induced by the gene therapy, resulting in marked improvements in total hemoglobin, Dr. Kanter reported. "Even more exciting than the laboratory findings, many individuals have also reported significant improvements in terms of pain intensity, fatigue, and the degree to which pain interfered with daily life," said Dr. Kanter. The process of administering lovo-cel requires patients to undergo an autologous stem cell transplant (a transplant that uses a patient's own stem cells instead of those from a donor) and uses conditioning chemotherapy to remove the old bone marrow and prepare the space for the new, modified stem cells. Side effects were common and consistent with conditioning chemotherapy including mouth sores and low blood counts. One patient was diagnosed with a blood cancer known as myelodysplastic syndrome. Scientists determined that the viral vector used for lovo-cel therapy did not cause the disorder; the patient also has not required any blood transfusions or experienced any vaso-occlusive events and continues to receive close monitoring. Overall, the study provides strong evidence that lovo-cel is effective at the genetic level to produce healthy (non-sickled) hemoglobin, reduce hemolysis (cell breakage), improve total hemoglobin, and prevent vaso-occlusive events over an extended period while also improving patient quality of life; however, Dr. Kanter and team cautioned that longer-term data will be needed to determine whether it also helps to prevent stroke, kidney disease, and other longer-term complications of SCD. To reduce health disparities commonly faced by people with SCD, Dr. Kanter added that it will also be important to work to address cost barriers and ensure equitable access to the therapy — as well as continuing care after patients receive it — if the therapy receives approval from the U.S. Food and Drug Administration. "We don't know the long-term effects yet, so we need to make sure that the patients who get this gene therapy also receive ongoing care," said Dr. Kanter. "We also want to make sure that the centers that are performing these therapies really understand SCD and are equipped to take care of people with SCD for the best possible outcomes." Dr. Kanter noted that the study has a relatively small sample size, was not randomized, and did not include people with severe renal disease, heart disease, or severe central nervous system vascular disease. The trial was funded by bluebird bio, developer of lovo-cel. This abstract will be presented by Julie Kanter of the University of Alabama, Birmingham in an oral presentation on Monday, December 11, 2023, at 4:30 p.m. Pacific time in Hall A (San Diego Convention Center). Extended use of hydroxyurea with optimal dosing found to be safe and effective in children with sickle cell anemia in Africa 6: Hydroxyurea Dose Optimization Is Safe and Improves Outcomes for Children with Sickle Cell Anemia Living in Sub-Saharan Africa: The Reach Experience Hydroxyurea is safe, well tolerated, and effective in Africa, according to the latest data from the Realizing Effectiveness Across Continents with Hydroxyurea (REACH) trial. REACH is the largest trial to test hydroxyurea in children anywhere in the world and among the first to test its feasibility in real-world settings in Africa, where children with sickle cell anemia face additional health risks such as malnutrition and malaria that are less prevalent elsewhere. The new data align with findings reported earlier in the study and, now with an average follow-up of over seven years, increase confidence that hydroxyurea treatment can be feasibly maintained in African settings with good safety and efficacy in the long term. In addition, the study underscores the importance of achieving the optimal dose of hydroxyurea, as higher doses lead to the best clinical responses. "It's really exciting to see that the optimal dose is safe and effective," said Banu Aygun, MD, Cohen Children's Medical Center of New York, and the study's lead author. "It suggests that we should advocate for giving the best dose to children living in Africa just like we are doing here in the United States." Newborns are routinely screened for SCD in the United States, where there are currently about 100,000 affected individuals, most of whom have access to treatments such as hydroxyurea, which reduces SCD complications by increasing the production of fetal hemoglobin. In Africa, where it is estimated that over 300,000 babies are born with sickle cell each year, newborn screening programs are just beginning to be established and the vast majority of children do not have access to hydroxyurea treatment. For the REACH trial, researchers worked with local partners in Angola, the Democratic Republic of Congo, Kenya, and Uganda to administer hydroxyurea to a total of 606 children with a genetic subtype of SCD known as sickle cell anemia, 86% of whom still remain on treatment an average of over seven years later. Participants received a low fixed dose of 15 to 20 mg/kg/day initially to ensure safety. Once safety was established, the dosing was raised and then further optimized to allow each patient to receive the highest dose they could tolerate safely. After this optimization process, the average dose reached about 27.5 mg/kg/day, which is similar to the optimal dosage of 25 to 30 mg/kg/day that is standard in the United States. These extended REACH results show both safety and strong efficacy, especially when comparing the optimized dose with the lower initial fixed dose. Laboratory responses including various measures of hemoglobin content in the blood improved with increasing dosage, while the rate of events including vaso-occlusive episodes, acute chest syndrome, enlargement of the spleen, stroke, transfusions, malaria, non-malarial infections, and deaths decreased. There were few safety concerns and a low overall rate of dose-related toxicities. Researchers say hydroxyurea is well suited for use in Africa because it is a daily pill that does not require refrigeration, is relatively inexpensive, and has a long track record of benefits. However, the feasibility of its implementation in Africa was uncertain until this study because of concerns about cost, how well the treatment would work in populations facing risks that have not been previously studied such as malnutrition and high rates of malaria, and whether issues such as lack of transportation, language barriers, and political instability would hinder families' ability to access clinics. Based on the results, researchers say there is now good evidence that hydroxyurea treatment at optimal dosing is feasible and beneficial for children living with sickle cell anemia in Africa. "Many newborn screening programs are coming out [now], and we know for newborn screening programs, it's not enough to diagnose a condition if you can't tie it to a treatment," said Dr. Aygun. "If we are diagnosing children with sickle cell anemia, we have to be able to offer hydroxyurea to them." Banu Aygun of Cohen Children's Medical Center will present this study in the Plenary Scientific Session on Sunday, December 10, 2023, at 2:00 p.m. Pacific time in Hall A (San Diego Convention Center). Researchers trace lifelong impacts of folate deficiency during early development 5: Metabolic Programming of Hematopoietic Stem Cell Function By Prenatal Folate For decades, pregnant women have been advised to consume enough of the B-vitamin folic acid, or folate, to prevent neural tube defects in their babies, and many foods in the U.S. are fortified with folate for this reason. However, there has been little understanding of how folic acid might affect prenatal development in other ways. Now, a new study conducted in mice has uncovered some of the mechanisms by which exposure to too little — or too much — folate in the womb can affect a person's health and susceptibility to disease into adulthood. The study examines the relationship between prenatal folate availability and metabolic programming of hematopoietic, or blood, stem cells (HSCs), the stem cells that give rise to all blood and immune cells in the adult body. When functioning properly, HSCs ensure the body has the right types and amounts of blood and immune cells. "Our study shows how manipulation of nutrients during early development can shape the function of the adult blood system by programming blood stem cells during development," said Brian Krum, MSc, a PhD student at the University of Utah, and the study's lead author. "These changes persist into adulthood where they have permanent effects on the hematopoietic system and also potentially affect immune function and disease risk." Previous studies have shown that folate helps regulate red blood cell production; in adults, low-circulating folate can cause anemia. The new study is the first to examine how folate levels in a pregnant mother affect HSCs in her children. The results reveal that prenatal folate exposure can affect HSCs and their function into adulthood. The researchers assessed HSC function in the offspring of mice that were fed diets that were folate deficient, folate sufficient, or folate supplemented during pregnancy. The results showed that HSCs from adult mice that were exposed to folate deficiency during fetal development had poorer performance in producing all types of blood and immune cells, while those that were exposed to excess folate during development overproduced all the same blood and immune cells. Tracing the metabolic pathways involved, the researchers found evidence that mitochondrial dysfunction was instrumental in driving the effects of folate deficiency on HSCs. Dysregulation of mitochondrial metabolism was evident in HSCs during fetal development and persisted into adult HSCs, suggesting that sustained metabolic defects are a key driver of the underlying dysfunction. For pregnant women, researchers said the findings underscore the need to address folate deficiency, which is common in lower-resourced countries where people may not have access to enough folate-rich foods. While folate deficiency is rare in countries like the U.S. where food is fortified with folate and folic acid supplements are often taken during pregnancy, Krum noted that consuming excess folate may also have implications for blood and immune function. The study findings are also relevant to understanding the interactions between nutrition and anti-folate chemotherapy drugs. Researchers suggested future studies illustrating the metabolic aspects of HSC programming by folate might help identify novel pathways and targets to more selectively target folate metabolism in blood cancers, particularly pediatric leukemias, in order to achieve the best therapeutic benefit while minimizing toxicities. Brian Krum of the University of Utah will present this study during the Plenary Scientific Session on Sunday, December 10, 2023, at 2:00 p.m. Pacific time in Hall A (San Diego Convention Center). Emicizumab found safe and effective for preventing bleeding in infants with Hemophilia A 505: Emicizumab Prophylaxis in Infants with Severe Hemophilia A without Factor VIII Inhibitors: Results from the Primary Analysis of the HAVEN 7 Study In a new study, infants with severe hemophilia A who started receiving emicizumab in the first few months of life experienced few bleeding events, no other serious hemophilia complications, and no serious treatment-related adverse events. Researchers say the results offer reassurance that this hemophilia drug, which was previously tested mostly in older children and adults, is safe and effective for use in infants too. The drug could fill a significant gap for babies born with hemophilia A, who generally cannot receive factor VIII infusions to replace the clotting agent that their bodies do not make naturally, due to challenges with administering regular intravenous infusions in young infants (including challenges with venous access and the need for central venous access devices). Without factor VIII infusions or other therapies, these babies can be vulnerable to uncontrolled bleeding and damage to joints and organs, including bleeding in the brain. "Emicizumab proved to be highly efficacious in these infants in preventing all bleeds, traumatic bleeds, and spontaneous bleeding, and it was well tolerated," said Steven Pipe, MD, of the University of Michigan, the study's lead author. "I think this is going to be adopted broadly [as a prophylactic agent in infants]." Factor VIII infusions are a mainstay of hemophilia A treatment, particularly for stemming severe bleeding or controlling bleeding during surgery. However, these infusions can become less effective if patients develop antibodies that inhibit factor VIII, something that grows more likely with increased exposure to factor VIII. Emicizumab is an effective prophylactic therapy even in the presence of factor VIII inhibitors, Dr. Pipe explained. Since its approval as a first-line hemophilia therapy in 2017, emicizumab has been increasingly adopted as a prophylactic drug to prevent bleeding and reduce the number of factor VIII infusions patients require. Until now, there has been little data on the use of emicizumab in young babies. For the study, researchers administered the drug to 55 infants with hemophilia A starting at a median age of four months and continuing for a median of just under two years and a minimum of one year. After an initial loading period of four weekly injections, parents administered the drug at home via subcutaneous injection every two weeks. Throughout the study, over half of the study participants (54.5%) had no bleeds requiring treatment. All treated bleeding events were related to trauma such as scrapes and falls; no participants had bleeding in the brain or spontaneous bleeds requiring treatment. Laboratory tests showed that most participants were able to maintain therapeutic concentrations of the study drug in their bodies and none developed antidrug antibodies. Adverse events such as fevers and infections were common, which was expected given that infants frequently experience minor illnesses. The only adverse events that were considered treatment-related were low-grade reactions (localized redness of the skin) at the injection site, which occurred in 16.4% of participants and were temporary, said Dr. Pipe. Researchers noted that more research will be needed to gauge any long-term effects of emicizumab use in babies, including whether it helps reduce the use of factor VIII and consequently the development of factor VIII inhibitors. In the meantime, Dr. Pipe suggested that emicizumab represents a good prophylactic option for babies, especially during the first year when administering factor VIII as a prophylactic therapy is often not feasible. "Many people would call this a game-changer as far as clinical practice is concerned," said Dr. Pipe. "If you're a parent of an infant with hemophilia, to have a therapeutic option that you can get your baby started on as soon as possible just provides such reassurance for the family." Steven Pipe, University of Michigan, will present this study in an oral presentation on Sunday, Dec. 10, 2023, at 12:00 noon in room 29 (San Diego Convention Center). ### The American Society of Hematology (ASH) (hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH's flagship journal, Blood (bloodjournal.org) is the most cited peer-reviewed publication in the field, and Blood Advances (bloodadvances.org) is an open-access, online journal that publishes more peer-reviewed hematology research than any other academic journal worldwide. Two new journals will be joining the Blood Journals portfolio in 2024, Blood Neoplasia (bloodneoplasia.org) and Blood Vessels, Thrombosis & Hemostasis (bloodvth.org). Contact: Melissa McGue, ASH, [email protected] Kira Sampson, ASH, [email protected] Brianne Cannon, FleishmanHillard, [email protected] SOURCE American Society of Hematology